A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications

Abstract:

Currently, a psychologically based model is widely held to be the basis for the aetiology and treatment of chronic fatigue syndrome(CFS)/myalgic encephalomyelitis (ME)/systemic exertion intolerance disease (SEID). However, an alternative, molecular neurobiological approach is possible and in this paper evidence demonstrating a biological aetiology for CFS/ME/SEID is adduced from a study of the history of the disease and a consideration of the role of the following in this disease: nitric oxide and peroxynitrite, oxidative and nitrosative stress, the blood-brain barrier and intestinal permeability, cytokines and infections, metabolism, structural and chemical brain changes, neurophysiological changes and calcium ion mobilisation. Evidence is also detailed for biologically based potential therapeutic options, including: nutritional supplementation, for example in order to downregulate the nitric oxide-peroxynitrite cycle to prevent its perpetuation; antiviral therapy; and monoclonal antibody treatment. It is concluded that there is strong evidence of a molecular neurobiological aetiology, and so it is suggested that biologically based therapeutic interventions should constitute a focus for future research into CFS/ME/SEID.

Source: Monro JA, Puri BK. A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications. Mol Neurobiol. 2018 Feb 6. doi: 10.1007/s12035-018-0928-9. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29411266

Neurobiology of chronic fatigue syndrome

Abstract:

1. Chronic fatigue syndrome (CFS) is characterized by a new onset of significant fatigue for a period of six months or longer usually following an infection, injury or period of high stress.

2. The exact etiology of CFS is not known and a diagnostic test is not available. Hence, the diagnosis is made by exclusion of other explanations for the patient’s symptoms and by meeting the CDC research case definitions. Early studies supported an infectious or immune dysregulation hypothesis for the pathophysiology of CFS.

3. Subsequent studies documented that neurological, affective and cognitive symptoms also occur at high rates in CFS patients. Neuropsychological, neuroendocrine studies and brain imaging have now confirmed the occurrence of neurobiological abnormalities in most patients with CFS.

4. In this article, the authors review these findings in relation to the clinical neurobiology of CFS and their potential relevance to biological psychiatry.

 

Source: Gonzalez MB, Cousins JC, Doraiswamy PM. Neurobiology of chronic fatigue syndrome. Prog Neuropsychopharmacol Biol Psychiatry. 1996 Jul;20(5):749-59. http://www.ncbi.nlm.nih.gov/pubmed/8870062

 

Current studies on the neurobiology of chronic fatigue syndrome

Abstract:

Cytokines are soluble mediators which are released by activated immune cells during infection and inflammation. The possibility that fatigue is mediated by the effects of cytokines on the central nervous system is supported by several converging lines of evidence: 1) infusions of cytokines to immunocompromised patients induce flu-like symptoms including fatigue and malaise; 2) peripheral and central injection of cytokines to laboratory rodents induce sickness behaviour; 3) symptoms of sickness behaviour occurring during experimental infections can be abrogated by administration of anti-cytokine treatments; 4) although many pitfalls in the detection of cytokines still exist, patients afflicted with the chronic fatigue syndrome have been found in some studies to display instances of excessive production of cytokines.

Experimental studies have confirmed that cytokines are interpreted by the brain as internal signals for sickness. Furthermore, there is evidence that sickness is a motivation which reorganizes the organism’s priorities in face of this particular threat which is represented by infectious pathogens. The elucidation of the mechanisms that are involved in these effects and in particular, the role of the cytokines which are produced in the brain in response to peripheral immune stimuli and to stressors, should give new insight on the way sickness and recovery processes are organized in the brain.

 

Source: Dantzer R. Current studies on the neurobiology of chronic fatigue syndrome. Encephale. 1994 Nov;20 Spec No 3:597-602. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843056